Signal networks among organ/tissue in the disorder of phosphate homeostasis

成纤维细胞生长因子 23 (FGF23) 是一种骨源性激素，在近端肾小管细胞的磷酸盐 (Pi) 转运中发挥重要作用。 Klotho 与 FGF 受体形成特异性受体复合物，在远端肾小管中传递 FGF23 信号。 FGF23/klotho 信号传导导致近曲小管中钠依赖性 Pi 协同转运蛋白 (NaPi-II ) 的下调。 在本研究中，我们研究了 FGF23/klotho 系统下调肾 Pi 转运蛋白的机制以及骨细胞中 FGF23 的产生。我们发现近曲小管中的 klotho 表达是由多种条件诱导的。此外，PKC 灭活 NaPi-IIc 是转运蛋白 FGF23/klotho 依赖性下调的第一步。因此，肾骨轴中的 FGF23/klotho 信号传导对于 Pi 稳态至关重要。

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays an important role in phosphate (Pi) transport in the proximal tubular cells. Klotho forms a specific receptor complex with FGF receptor that transmits signaling of FGF23 in the distal tubules. FGF23/klotho signaling leads to down-regulation of sodium-dependent Pi cotransporter (NaPi-II ) in the proximal tubules. In the present study, we investigated the mechanisms of down-regulation of renal Pi transporter by FGF23/klotho system and the production of FGF23 in bone cells. We show that klotho expression in the proximal tubules is induced by several conditions. Furthermore, inactivation of NaPi-IIc by PKC is the first step of FGF23/klotho dependent down-regulation of the transporters. Thus, FGF23/klotho signaling in the kidney-bone axis is essential for Pi homeostasis.